title: Association of prostate cancer risk Loci with disease aggressiveness and prostate cancer-specific mortality.
abstract: Genome-wide association studies have detected more than 30 inherited prostate cancer risk variants. While clearly associated with risk, their relationship with clinical outcome, particularly prostate cancer-specific mortality, is less well known. We investigated whether the risk variants are associated with various measures of disease aggressiveness and prostate cancer-specific mortality. In a cohort of 3,945 men of European ancestry with prostate cancer, we genotyped 36 single nucleotide polymorphisms (SNP): 35 known prostate cancer risk variants and one SNP (rs4054823) that was recently reported to be associated with prostate cancer aggressiveness. The majority of subjects had a diagnosis of prostate cancer between 1995 and 2004, and the cohort included a total of 580 prostate cancer-specific deaths. We evaluated associations between the 36 polymorphisms and prostate cancer survival, as well as other clinical parameters including age at diagnosis, prostate-specific antigen (PSA) at diagnosis, and Gleason score. Two SNPs, rs2735839 at chromosome 19q13 and rs7679673 at 4q24, were associated with prostate cancer-specific survival (P = 7 × 10(-4) and 0.014, respectively). A total of 12 SNPs were associated with other variables (P < 0.05): age at diagnosis, PSA at diagnosis, Gleason score, and/or disease aggressiveness based on D'Amico criteria. Genotype status at rs4054823 was not associated with aggressiveness or outcome. Our results identify two common polymorphisms associated with prostate cancer-specific mortality.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Pomerantz
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Gwo-Shu Mary
authors.initials: GS
authors.lastname: Lee
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Carolyn
authors.initials: C
authors.lastname: Evan
authors.forename: Gillian
authors.initials: G
authors.lastname: Petrozziello
authors.forename: Mari
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen